Ashleigh Kropp, Kazem Asadollahi, Jamie A. Stapleton, Luka Simsive, Pok Man Leung, Rachel L. Darnell, Christopher K. Barlow, Benjamin G. Hartmann, Nicholas D. J. Yates, Tasha Lumbantobing, Daniel R. Fox, Chris Greening, Oleksii Zdorevskyi, Vivek Sharma, James N. Blaza, Alison Parkin, Rhys Grinter
{"title":"Quinone-transporting filaments expand bioenergetic capacity in Gram-positive Bacillota","authors":"Ashleigh Kropp, Kazem Asadollahi, Jamie A. Stapleton, Luka Simsive, Pok Man Leung, Rachel L. Darnell, Christopher K. Barlow, Benjamin G. Hartmann, Nicholas D. J. Yates, Tasha Lumbantobing, Daniel R. Fox, Chris Greening, Oleksii Zdorevskyi, Vivek Sharma, James N. Blaza, Alison Parkin, Rhys Grinter","doi":"10.1038/s41564-026-02450-z","DOIUrl":"10.1038/s41564-026-02450-z","url":null,"abstract":"Cellular respiration depends on transferring electrons to hydrophobic quinones in membrane bilayers, meaning bioenergetic capacity is constrained by available membrane surface area. While Gram-negative bacteria expand this capacity through internal membrane invaginations and eukaryotes use membrane-bound organelles, whether Gram-positive bacteria have alternative capacity-generating mechanisms is unknown. Here we show that Bacillus subtilis forms a quinone-transporting pseudomembrane composed of filaments of the NADH dehydrogenase Ndh and the quinone-transporting protein Ncp. Cryo-EM, lipidomics and molecular dynamics reveal that Ndh and Ncp co-assemble with lipids into a 4:4 stoichiometric complex with a solvent-excluded hydrophobic lumen containing phospholipids, which sequesters quinones. These complexes further assemble into filaments, linking chambers into a continuous conduit that amplifies quinone reduction. Phylogenetic analysis suggests that this capacity is widespread in Bacillota. Quinone-transporting filaments thus reveal a strategy to expand the quinone pool and bioenergetic capacity while occupying minimal membrane space. Bacillus subtilis Ncp and NADH dehydrogenase form tube-like filaments with phospholipid-lined chambers that associate with quinones, which can expand bioenergetic capacity and support respiratory electron transfer.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2543-2561"},"PeriodicalIF":18.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02450-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148769134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tomer Antman, Ohad Lewin-Epstein, Tamir Yerushalmi, Yonatan S. Broder, David Zeevi
{"title":"Global microbial DNA signatures of temperature and nutrient limitation across ecosystems","authors":"Tomer Antman, Ohad Lewin-Epstein, Tamir Yerushalmi, Yonatan S. Broder, David Zeevi","doi":"10.1038/s41564-026-02451-y","DOIUrl":"https://doi.org/10.1038/s41564-026-02451-y","url":null,"abstract":"Microbial genomes continuously adapt to environmental conditions, but identifying universal signatures of adaptation remains challenging. Here we show that environmental temperature can be accurately predicted across ecosystems from DNA composition alone (R2 = 0.75), using tetranucleotide frequencies from 1,235 marine and soil metagenomes and a machine learning approach. This predictive signal was also apparent within individual taxa, consistent with a fundamental temperature-associated signature. By contrast, GC content exhibited opposite correlations with temperature in soil (positive) and marine (negative) environments. This phenomenon was probably driven by differences in nutrient availability, as GC content increases with nutrients while nutrients decrease with temperature in marine samples. By integrating these observations, we identified specific tetranucleotides, with 50% GC, that displayed consistent and robust temperature correlations across environments and may have contributed to the stability of predictions. This work highlights metagenome-wide DNA–temperature associations, relevant for understanding microbial community responses to global changes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"16 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yumary M. Vasquez, Tiago Nardi, Gbocho Masato Terasaki, Petra Byl, Tomáš Brůna, Juan C. Villada, Miguel F. Romero-Gutiérrez, Thomas Mock, Timothy Y. James, GVMAGs data consortium, Tanja Woyke, Frederik Schulz
{"title":"Genomic catalogue of giant viruses reveals expanded diversity and functional potential","authors":"Yumary M. Vasquez, Tiago Nardi, Gbocho Masato Terasaki, Petra Byl, Tomáš Brůna, Juan C. Villada, Miguel F. Romero-Gutiérrez, Thomas Mock, Timothy Y. James, GVMAGs data consortium, Tanja Woyke, Frederik Schulz","doi":"10.1038/s41564-026-02435-y","DOIUrl":"10.1038/s41564-026-02435-y","url":null,"abstract":"Nucleocytoplasmic large DNA and Mirusviricota viruses exhibit taxonomic richness which continually expands due to metagenomic sequencing. Here we curate a database of giant virus metagenome-assembled genomes (GVMAGs V2), comprising 8,508 species-level representatives from 18,727 GVMAGs, a sixfold increase from the previous giant virus phylogenetic frameworks. Phylogenomics revealed 712 previously undescribed genera, 13 previously unknown viral families and an order we propose named Mycodnavirales. By accounting for alternative and custom genetic codes, we improved gene calling in over 1,300 GVMAGs, enabling more accurate identification of protein-coding genes. Database mining uncovered putative endogenous viral elements in hosts spanning algae, fungi and parasitic protists, highlighting that giant virus integration is widespread and evolutionarily persistent. Protein-level analysis revealed enriched genes for pollutant degradation in Algavirales and widespread biosynthetic gene clusters linked to antimicrobial-like and antibiotic resistance gene-like activity. This public resource will serve as a foundation for expanding giant virus diversity, uncovering virus–host interactions and exploring viral evolution. This curated genome-resolved, metagenomic resource expands the known diversity of Nucleocytoviricota and Mirusviricota lineages.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2634-2646"},"PeriodicalIF":18.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02435-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jasper B. Gomez, Jeffrey E. Barrick, Christopher M. Waters
{"title":"Phage-encoded contingency loci enable bet-hedging against host defence mechanisms","authors":"Jasper B. Gomez, Jeffrey E. Barrick, Christopher M. Waters","doi":"10.1038/s41564-026-02445-w","DOIUrl":"10.1038/s41564-026-02445-w","url":null,"abstract":"Bacteriophages are the most diverse biological entities on Earth, but the processes influencing the evolution of genomic diversity in phages are poorly understood. Here, we show that phage genomes contain contingency loci, hypermutable DNA regions that promote reversible frameshift mutations through DNA polymerase slippage on simple sequence repeats. Contingency loci have been extensively described in bacteria, archaea and eukaryotes, yet are understudied in phages. We use experimental evolution and genome sequencing to demonstrate that contingency loci in E. coli phages T2 and T4 reversibly generate genomic and phenotypic heterogeneity in progeny that allow them to hedge their bets against host defences. We find that simple sequence repeats are widespread in diverse E. coli phages and vary in abundance across genes with different functions. Collectively, our study describes a previously unappreciated facet of phage replication in which mutagenic simple sequence repeats drive genetic diversification and population heterogeneity, allowing phages to exploit hosts despite varying defence mechanisms. Diverse E. coli phage genomes have hypermutable DNA regions that promote reversible frameshift mutations through DNA polymerase slippage, generating population heterogeneity that enables host exploitation.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2515-2524"},"PeriodicalIF":18.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie-Madlen Pust, Ahmed M. T. Mohamed, Martin Stražar, Aranzazu Arias-Rojas, Edward Cunningham-Oakes, Eric M. Brown, Amanda Bumber, Gleb Pishchany, Chenhao Li, Ashwin N. Ananthakrishnan, Alistair C. Darby, Hera Vlamakis, Damian R. Plichta, Ramnik J. Xavier
{"title":"Antisense transcription reveals disease-associated adaptations in the human gut microbiome","authors":"Marie-Madlen Pust, Ahmed M. T. Mohamed, Martin Stražar, Aranzazu Arias-Rojas, Edward Cunningham-Oakes, Eric M. Brown, Amanda Bumber, Gleb Pishchany, Chenhao Li, Ashwin N. Ananthakrishnan, Alistair C. Darby, Hera Vlamakis, Damian R. Plichta, Ramnik J. Xavier","doi":"10.1038/s41564-026-02442-z","DOIUrl":"10.1038/s41564-026-02442-z","url":null,"abstract":"The gut microbiome is a dynamic ecosystem in which microorganisms constantly adjust their transcriptional programmes. Here we developed metastrand, a framework that integrates strand-aware metatranscriptomics and metagenomics to quantify mRNAs and antisense RNAs (asRNAs) in complex microbial communities at gene-level resolution. In inflammatory bowel disease (IBD), microbial asRNA programmes converged across patients during active disease, correlated with faecal metabolites and calprotectin levels and remained stable during persistent inflammation, highlighting their potential as biomarkers of inflammatory activity in the gut. These programmes involved antisense-to-sense transcriptional shifts at insertion sequence elements with functionally diverse passenger genes and preceded their detection at new genomic locations, linking asRNA dynamics to structural genome rearrangements and redistribution of adaptive functions under selective pressure. Similar dynamics were observed in a mouse model of colitis, oxidative stress in vitro and in patients with pathogen-confirmed gastroenteritis, establishing asRNAs as an important dimension of microbial adaptation in health and disease. Metastrand integrates strand-aware metatranscriptomic and metagenomic data to distinguish microbial sense from antisense transcription at gene-level resolution, and a use case study highlights the importance of antisense RNAs in understanding the microbial dynamics in inflammatory bowel disease.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2464-2477"},"PeriodicalIF":18.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bacterial symbionts and the lightness of being a prokaryote","authors":"Silvia Bulgheresi","doi":"10.1038/s41564-026-02440-1","DOIUrl":"10.1038/s41564-026-02440-1","url":null,"abstract":"Silvia Bulgheresi muses on how studying bacterial symbionts of worms and mammals made her question whether the absence of a nucleus enables cellular freedom, potentiating architectural innovation and functional adaptation.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2389-2390"},"PeriodicalIF":18.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonah B Sacha, Tracy Ordonez, Shilpi Pandey, Gabriela Webb, Philip Barnette, Cleiton Pessoa, Matthew C Humkey, Jason Reed, Anden Morehead, Jennifer K Watanabe, Jodie L Usachenko, Shrivaas Vijayan, Altair Fazio, Heather Sidener, Anne D Lewis, Gabrielle Pastenkos, Sohita Ojha, Aaron Barber-Axthelm, Bella Swan, Rachele Bochart, John R Mascola, Amarendra Pegu, Emily J Fray, Rachael M Wolters, Janet D Siliciano, Robert F Siliciano, Scott G Hansen, Koen K A Van Rompay, Ann J Hessell, Nancy L Haigwood
{"title":"Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV.","authors":"Jonah B Sacha, Tracy Ordonez, Shilpi Pandey, Gabriela Webb, Philip Barnette, Cleiton Pessoa, Matthew C Humkey, Jason Reed, Anden Morehead, Jennifer K Watanabe, Jodie L Usachenko, Shrivaas Vijayan, Altair Fazio, Heather Sidener, Anne D Lewis, Gabrielle Pastenkos, Sohita Ojha, Aaron Barber-Axthelm, Bella Swan, Rachele Bochart, John R Mascola, Amarendra Pegu, Emily J Fray, Rachael M Wolters, Janet D Siliciano, Robert F Siliciano, Scott G Hansen, Koen K A Van Rompay, Ann J Hessell, Nancy L Haigwood","doi":"10.1038/s41564-026-02444-x","DOIUrl":"https://doi.org/10.1038/s41564-026-02444-x","url":null,"abstract":"<p><p>Lack of access to antiretroviral therapy (ART) leads to the transmission of human immunodeficiency virus in ~120,000 children annually, emphasizing the need for new strategies to prevent lifelong infection. Here in an infant rhesus macaque model of peripartum oral infection, we show that broadly neutralizing antibodies directed to the viral envelope protein were insufficient to prevent latent reservoir establishment, independent of daily ART. Blockade of the human immunodeficiency virus co-receptor CCR5 via the antibody leronlimab also failed to prevent reservoir establishment, but it significantly reduced reservoir seeding in lymphoid and gastrointestinal tissues. Following the treatment of infants with viraemia at 72 h post-infection with the combination of broadly neutralizing antibodies, ART and leronlimab, no subsequent evidence of replicating or latent virus and antiviral immunity was observed 1 year after treatment interruption. These findings suggest a synergy between broadly neutralizing antibodies, ART and CCR5 blockade for preventing viral reservoir establishment and offer potential improvements over current therapies for newborns exposed to human immunodeficiency virus.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Landon J. Getz, Amy L. Qian, Y. Vivian Liu, Sam R. Fairburn, Mahnoor S. Butt, Yan-Jiun Lee, Peter R. Weigele, Karen L. Maxwell
{"title":"Antiviral defence is a conserved function of diverse bacterial DNA glycosylases","authors":"Landon J. Getz, Amy L. Qian, Y. Vivian Liu, Sam R. Fairburn, Mahnoor S. Butt, Yan-Jiun Lee, Peter R. Weigele, Karen L. Maxwell","doi":"10.1038/s41564-026-02441-0","DOIUrl":"10.1038/s41564-026-02441-0","url":null,"abstract":"Bacteria are frequently attacked by viruses, known as phages, and rely on diverse defence systems to survive. While phages can evade defences by covalently modifying their DNA, these non-canonical nucleobases create molecular signatures that bacteria can exploit. Here, using structure-guided discovery, we identified two widespread families of anti-phage DNA glycosylases, Dag1 and Dag2. Although DNA glycosylases are classically associated with DNA repair, Dag1 and Dag2 act as antiviral effectors that selectively target phages carrying modified guanine bases. Guided by the conserved glycosylase fold, we uncovered numerous defence-associated glycosylases that collectively form a diverse repertoire of enzymes targeting chemically modified phage DNA. We further identified a distinct glycosylase superfamily that protects against phages carrying modified thymidine bases. Together, these findings establish DNA glycosylases as a versatile class of bacterial immune proteins and highlight structure-guided discovery as a powerful strategy for uncovering hidden antiviral defences. DNA glycosylases, typically used for DNA repair, can also protect bacteria against phages that would otherwise evade host immunity by incorporating modified bases into their genomes.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2589-2600"},"PeriodicalIF":18.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic surveillance reveals co-occurrence of Plasmodium falciparum drug resistance variants across diverse transmission settings in Ethiopia","authors":"Alemayehu Letebo, Leen N. Vanheer, Mengst Engdaw, Legesse Alamerie Ejigu, Dawit Hailu Alemayehu, Jimma Dinsa Deressa, Bethlehem Adnew, Abaysew Ayele, Migbaru Keffale Bezabih, Mulugeta Demisse, Tamrayehu Seyoum, Meklit Shiferaw, Heven Sime, Atsbeha Gebreegziabxier Weldemariam, Amanuel Shimelash, Elias B. Tafa, Wakweya Chali, Lina Alemayehu, Fikregabrail Aberra Kassa, Ayalew Jejaw Zeleke, Tajudin Abdurhaman Hamza, Abel Beliyu Tamirat, Tadesse Misganaw, Alayu Bogale, Zufan Yiheyis Abriham, Yasin Nasir, Gutema Jebessa, Metmiku Yohannes, Betelhem Akililu Kebede, Matiwos Kidane Ayele, Melat Abdo, Getinet Habtamu, Addisu Gizat, Jody Phelan, Bryce Matlock, David A. Fidock, Susana Campino, Ashenafi Assefa, Cristian Koepfli, Fekadu Massebo, Fitsum G. Tadesse","doi":"10.1038/s41564-026-02420-5","DOIUrl":"10.1038/s41564-026-02420-5","url":null,"abstract":"The emergence of antimalarial drug resistance threatens malaria control and elimination efforts in Africa. Ethiopia, once a success story in case reduction, is now experiencing a resurgence. Here we examine key drug resistance genes (Pfmdr1, Pfcrt, Pfk13, Pfdhfr and Pfdhps) and mitochondrial genomes from 605 Plasmodium falciparum isolates collected across 15 districts in Ethiopia with varying transmission intensity and Plasmodium vivax co-endemicity. Although chloroquine was withdrawn for P. falciparum long ago, it remains the first-line treatment for P. vivax; this overlapping use may shape selection pressure in co-endemic settings that influences resistance markers to artemether–lumefantrine, the current first-line therapy for P. falciparum. A dominant PfMDR1 NFSND haplotype, associated with reduced lumefantrine susceptibility, was identified alongside near fixation of the chloroquine-resistant PfCRT CVIET haplotype in specific areas. Concerningly, PfK13 variants associated with partial artemisinin resistance, R622I (10%), A675V (1.7%) and P441L (1.1%), were expanding. Multilevel models demonstrated robust, independent associations of R622I with PfCRT CVIET and PfDHFR AICNI, while ecological predictors were weaker and less consistent. These findings highlight genetic co-occurrence of Pfcrt and Pfk13 mutations in P. vivax–P. falciparum co-endemic settings and can inform antimalarial policy in Ethiopia. Artemisinin partial resistance is expanding in Ethiopia and, together with a dominant lumefantrine-tolerant PfMDR1 haplotype and co-occurring Pfcrt and Pfk13 mutations, defines a complex multidrug-resistance landscape that may reflect overlapping treatment pressures in Plasmodium vivax and Plasmodium falciparum co-endemic settings.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 9","pages":"2577-2588"},"PeriodicalIF":18.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02420-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}